title: Peroxisome proliferator-activated receptor-γ agonist pioglitazone suppresses experimental autoimmune uveitis.
abstract: Peroxisome proliferator-activated receptor (PPAR)-γ agonists are clinically used as anti-diabetes agents. Recent research has discovered that an anti-inflammatory effect of PPAR agonist may have the potential to treat autoimmune disease. In the present study, we investigated the anti-inflammatory effects of PPAR-γ agonist, pioglitazone, on murine model of endogenous uveitis. Experimental autoimmune uveoretinitis (EAU) was induced by immunizing C57BL/6 mice with human interphotoreceptor retinoid binding protein-derived peptide (1-20). Pioglitazone or vehicle was injected intravenously from day -1 (whole phase treatment) or day 8 (effector phase study) until day 20. Severity of EAU was assessed clinically and pathologically on day 21. Immunological status was assessed by measuring intraocular inflammatory factors, and activation and regulatory markers of CD4(+) T cells in draining lymph nodes (LNs). Treatment with pioglitazone suppressed both whole-phase and effector-phase of EAU. In effector-phase treatment, intraocular concentrations of TNF-α and IL-6 were significantly suppressed, and CD4(+)Foxp3(+) regulatory T cells and CD4(+)CD62L(high) naïve T cells increased in draining LNs, although there were no differences in CD4(+)CD44(high) effector T cells and IL-17 producing CD4(+) T cells between pioglitazone- and vehicle-treated mice. Administration of pioglitazone before and after the onset of EAU significantly reduced disease severity. The present results suggest that pioglitazone may be a novel therapeutic agent for endogenous uveitis.
authors.affiliation: Department of Ophthalmology, Tokyo Medical University, 6-7-1 Nishishinjuku, Shinjuku-ku, Tokyo 160-0023, Japan. Electronic address: yoko-okunuki@nifty.com.
authors.forename: Yoko
authors.initials: Y
authors.lastname: Okunuki
authors.forename: Yoshihiko
authors.initials: Y
authors.lastname: Usui
authors.forename: Hayate
authors.initials: H
authors.lastname: Nakagawa
authors.forename: Kazuki
authors.initials: K
authors.lastname: Tajima
authors.forename: Ryusaku
authors.initials: R
authors.lastname: Matsuda
authors.forename: Shunichiro
authors.initials: S
authors.lastname: Ueda
authors.forename: Takaaki
authors.initials: T
authors.lastname: Hattori
authors.forename: Takeshi
authors.initials: T
authors.lastname: Kezuka
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Goto
mesh_terms: D000818:Animals; D001327:Autoimmune Diseases / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D004195:Disease Models, Animal; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000627:therapeutic use; D007113:Immunity, Innate / Q000187:drug effects*; D007262:Infusions, Intravenous; D051379:Mice; D008810:Mice, Inbred C57BL; D047495:PPAR gamma / Q000819:agonists*; D000077205:Pioglitazone; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000378:metabolism; D045162:Thiazolidinediones / Q000008:administration & dosage / Q000627:therapeutic use*; D014605:Uveitis / Q000188:drug therapy / Q000276:immunology / Q000473:pathology
chemical_list: D007004:Hypoglycemic Agents; D047495:PPAR gamma; D045162:Thiazolidinediones; D000077205:Pioglitazone
keywords: Foxp3; experimental autoimmune uveitis; pioglitazone; proliferator-activated receptor-gamma